1. Field of the Invention
The invention relates generally to methods for processing ultra-high molecular weight polyethylene for use as a bearing surface. More particularly, the invention relates to methods for processing ultra-high molecular weight polyethylene for use as a bearing surface in artificial joints.
2. Related Art
Ultra-high molecular weight polyethylene (UHMWPE) is the most commonly used bearing material in total joint replacements and was introduced by John Charnley in the early 1960s (The UHMWPE Handbook, edited S. Kurtz, Elsevier, 2004). Since then, a wide variety of applications have been developed in the total joint arthroplasty, as a result of the material's high toughness and good mechanical properties. Although “conventional” UHMWPE has an excellent clinical record, the maximum lifetime of implant systems is restricted due to the wear particles released from the UHMWPE bearing surface (Willert H. G., Bertram H., Buchhorn G. H., Clin Orthop 258, 95, 1990). These wear particles can induce an osteolytic response in the human body leading to local bone resorption and eventually to aseptic loosening of the artificial joint.
A second problem associated with conventional, gamma-sterilized UHMWPE (2.5-4.0 Mrad; S. Kurtz, The UHMWPE Handbook, Elsevier, 2004), is the oxidative degradation that occurs during shelf ageing. Degradation occurs when the energy of the gamma rays is sufficient to break some of the carbon-carbon or carbon-hydrogen bonds of the polyethylene chains resulting in the formation of free radicals. The amount of free radicals can be measured, for example, by electron spin resonance measurements (ESR).
A standard gamma-sterilized (3 Mrad) UHMWPE implant has a free radical content of 1.46 E+18 g−1 (see free radical content chart in the Examples section below). These radicals partially recombine but some of them are long-living and can react with oxygen present in, or diffusing into, packaging surrounding the implant (Costa L., Jacobson K., Bracco P., Brach del Prever E. M., Biomaterials 23, 1613, 2002). The oxidative degradation reactions lead to embrittlement of the material and therewith reduce the mechanical properties of the material and might lead to fracture of the implant (Kurtz S. M., Hozack W., Marcolongo M., Turner J., Rimnac C., Edidin A., J Arthroplasty 18, 68-78, 2003).
In the 1970s, highly crosslinked UHMWPEs were introduced with the intention of improving the wear resistance of the material (Oonishi H., Kadoya Y., Masuda S., Journal of Biomedical Materials Research, 58, 167, 2001; Grobbelaar C. J., du Plessis T. A., Marais F., The Journal of Bone and Joint Surgery, 60-B, 370, 1978). The UHMWPE materials were gamma irradiated at high doses up to 100 Mrad. In contrast, to gamma sterilize UHMWPE radiation dosages generally range between 2.5 and 4.0 Mrad. The high doses of gamma irradiation on UHMWPE were used to promote the crosslinking process in the material and thereby increase the wear resistance. However, the free radical amount on the polyethylene chains is generally either not reduced or only locally reduced. Therefore these highly crosslinked materials are prone to the same oxidative degradation during shelf ageing or in-vivo use as the gamma-sterilized UHMWPE.
Radiation crosslinking of unstabilized UHMWPE leads to an increase of the number of free radicals and therefore to an undesired, critical oxidation of the material. Additionally, the mechanical properties of highly crosslinked UHMWPE decrease with increasing radiation dose (Lewis G., Biomaterials, 22, 371, 2001). These interactions between radiation dose and properties of unstabilized material that is not subjected to any post-irradiation heat treatment are qualitatively summarized in Table 1.
In Table 1, the benchmark is no radiation (0 Mrad). A “+” in Table 1 shows enhanced performance relative to the benchmark. A “−” in Table 1 shows inferior performance relative to the benchmark. Mc, the molecular weight between crosslinks, decreases with increased irradiation dose. Wear resistance was measured during a standard hip simulator test as described by McKellop (McKellop H. et al., J. Orth. Res., 17, 157, 1999). Mechanical properties were measured with a tensile test. Oxidation resistance was measured after artificial ageing according to ASTM F2003.
TABLE 1Effect of different radiation doses on selectedproperties of unstabilized UHMWPE that is not subjectedto any post-irradiation heat treatment.FreeWearradicalresistance*MechanicalOxidationRadiation dosecontent(~Mc)properties**resistance***0 Mrad0000 (e.g. 3 Mrad)↑+−− (e.g. 7 Mrad)↑↑++−−−− (e.g. 14 Mrad)↑↑↑+++−−−−−−
The relations between the radiation dose and the above mentioned properties is also demonstrated by the experiments, results of which are shown in the Examples below. Both free radical content and oxidation index increase with increasing radiation dose; a relation that was already found earlier (Collier J. P. et al., Clinical Orthopaedics and Related Research, 414, 289-304, 2003). The wear resistance, which is related to the molecular weight between crosslinks Mc (Muratoglu O. K. et al., Biomaterials, 20, 1463-1470, 1999), is substantially enhanced by higher radiation doses. Additionally, thermal treatment to reduce or eliminate the number of free radicals has been well known in the art for decades.
These processes can be subdivided into three groups. The first group is irradiation below the melting temperature followed by annealing. The second group is irradiation below the melting temperature followed by remelting. The third group is irradiation in the melt.
Irradiation below the melting temperature followed by annealing below the melting temperature (U.S. Pat. No. 5,414,049, EP0722973). The main disadvantage of this route is the fact that the UHMWPE chains still contain residual free macroradicals which lead to oxidative degradation (Wannomae K. K., Bhattacharyya S., Freiberg A., Estok D., Harris W. H., Muratoglu O. J., Arthroplasty, 21, 1005, 2006).
Irradiation below the melting temperature followed by remelting above the melting temperature (U.S. Pat. No. 6,228,900). The main disadvantage of this processing scheme is that compared with the annealing process, the mechanical properties are reduced by the remelting step (Ries M. D., Pruitt L., Clinical Orthopaedics and Related Research, 440, 149, 2005).
Irradiation in the melt (U.S. Pat. No. 5,879,400, Dijkstra D. J., PhD Thesis, University of Groningen, 1988). The disadvantage of this process is that the crystallinity is substantially reduced and therewith the mechanical performance.
Others have experimented with chemical antioxidants introduced into medical grade UHMWPE to obtain a wear resistant material that combines a good oxidative stability with sufficient mechanical properties. Most of the common antioxidants exhibit reduced or no biocompatibility, and therefore chemical substances already existing in the human body or in nutritional products were sought. In 1982, Dolezel and Adamirova described a procedure to increase the stability of polyolefins for medical implants against biological degradation in living organisms (CZ 221404). They added alpha-, beta-, gamma- or deltatocopherol (vitamin E), or a mixture thereof, to polyethylene resin and subsequently processed the resulting mixtures. However they did not attempt to crosslink the material to improve its wear resistance.
Recently, several groups established different processing procedures and combined the addition of substantial (0.1%-1.8% w/w) amounts of vitamin E with a radiation crosslinking step to improve the wear resistance of the material. Some of these investigators added substantial amounts of vitamin E prior to the consolidation of the UHMWPE powder (JP 11239611, U.S. Pat. No. 6,277,390, U.S. Pat. No. 6,448,315, WO0180778, WO 2005074619) followed by radiation crosslinking. Others diffused the liquid vitamin E into machined products after the irradiation step, occasionally with the aid of elevated temperatures (CA 256129, WO 2004064618, WO 2005110276, WO 2005074619). Addition of substantial amounts of Vitamin E prior to irradiation negatively affects the crosslinking efficiency of the material and limits the improvement of wear resistance (Oral E. et al., Biomaterials, 26, 6657, 2005).
Diffusion of vitamin E into UHMWPE products after irradiation also comprises several drawbacks: due to the diffusion-controlled doping of UHMWPE products, the depth of the vitamin E level remains uncontrolled, inhomogeneous and limited in its spatial dimensions. Although annealing steps after the actual doping process (which is also carried out at elevated temperatures) partially solve the problem of concentration gradients, the final amount of vitamin E in finished products remains unknown.
In addition, some of the above cited procedures are very cumbersome and cost-intensive. U.S. Pat. No. 6,277,390 describes a process using organic solvents, which run the risk of harming the human organism if not removed completely. U.S. Pat. No. 6,448,315 and CA 256129 describe the use of supercritical CO2, an expensive and difficult way to dope the UHMWPE with vitamin E. The diffusion-controlled doping of UHMWPE products described in WO2004064618 and 2005110276 is additionally very time-consuming (up to 48 hour soaking in vitamin E and 24 hour annealing are described).
Both above mentioned methods (post-irradiation heat treatment and the addition of substantial amounts of vitamin E) that were employed to improve the oxidative stability of highly crosslinked UHMWPE aimed towards an elimination of the free radicals.
As was done in Table 1 above, the effect of these two steps on selected properties of UHMWPE parts is shown is Table 2:
TABLE 2Expansion of Table 1 by two recent advances to increasethe oxidation resistance of highly crosslinked UHMWPE.FreeWearradicalresistanceMechanicalOxidationRadiation dosecontent(~Mc)propertiesresistance0 Mrad0000 (e.g. 3 Mrad)↑+−− (e.g. 7 Mrad)↑↑++−−−− (e.g. 14 Mrad)↑↑↑+++−−−−−− remelted0+++−−−0 annealed↑+++−−−− high vitE content0+−−0
Recently, the addition of trace amounts (<0.05%) of vitamin E prior to sintering was described to protect radiation crosslinked UHMWPE from oxidative degradation (Kurtz S. Mazzucco D. C., Siskey R. L., Dumbleton J., Manley M., Wang A., Trans. ORS 2007, 0020). However, only mechanical testing was conducted within this study and no attention was paid to the wear resistance of the material. According to Kurtz, at a dose of 7.5 Mrad, the highest amounts (0.0375 or 0.05%) of vitamin E have to be applied to retain a high oxidative stability. However, this combination between radiation dose and vitamin E content does not lead to a high wear resistant material. This can easily be concluded by looking at the Mc values of the “0.05% VitE 8 Mrad” sample in Examples below. Mc of this particular sample (5820 g/mol) is in the same order of magnitude as the “0.1% vitE 7 Mrad” (6000 g/mol) which showed only a slight decrease in the wear rate compared to a gamma-sterilized PE (see hip simulator data in Examples below).
Despite all these efforts, the desired combination between high wear resistance, mechanical properties and low oxidation index has not been achieved yet. Thus, there remains a need for an UHMWPE material for use in artificial joint replacements that combines excellent wear resistance, high oxidative stability and superior mechanical properties. These three material properties have not been combined to a satisfying level while maintaining a facile and cost-effective processing procedure.